The aim of this investigation is to examine cholesterol and cholestanol metabolism in patients with cerebrotendinous xanthomatosis (CTX), atherosclerosis and gallstones. Specifically, we shall continue to define the biochemical defect in the rare inherited lipid storage disease, CTX. Current evidence indicates that the defect is a block in the side chain oxidation of cholesterol to a carboxylic acid as part of the cholic acid synthetic pathway with the accumulation of 5 beta-cholestanol-3 alpha, 7 alpha, 12 alpha, 25-tetrol and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 24 XI-25-pentol. We shall investigate the role of these two bile alcohols and other analogs as precursors of cholic acid in normal man and determine the specific enzymatic defect in CTX liver that results in the accumulation of these bile alcohols. The importance of this wok is the potential discovery of a new pathway of cholic acid synthesis involving C25-hydroxy bile alcohols since current opinions indicate that cholic acid is formed only by C26-hydroxy compounds.